Structure of the human M1 muscarinic acetylcholine receptor bound to antagonist tiotropium

Structure

x-ray diffraction · 2 distinct chains · 73% helix, 3% strand (DSSP).

Ligands and binding sites

• 0HK · (1R,2R,4S,5S,7S)-7-{[hydroxy(dithiophen-2-yl)acetyl]oxy}-9,9-dimethyl-3-oxa-9-azoniatricyclo[3.3.1.0~2,4~]nonane · ligand · chains A
• Y01 · Cholesterol hemisuccinate · ligand · chains A
• EDO · 1,2-ethanediol · additive · 3 copies · chains A
• PGE · Triethylene glycol · additive · chains A, C
• GOL · Glycerol · additive · chains A

Binding sites are the residues within 4.5 Å of a ligand's heavy atoms.

Pockets

4 pockets found on a 1 Å grid, 2 with a druggability of 0.5 or more.

Interfaces

1 interface between chains.

• A–C · 483 Ų buried · 4 hydrogen bonds · protein-protein

Modifications

Observed in the structure: 2 disulfide (disulfide).

Compared structures

• 5CXV · Structure of the human M1 muscarinic acetylcholine receptor bound to antagonist Tiotropium · the same entry in another collection · chain A against A, TM-score 1.00
• P11229 · AlphaFold monomer V2.0 prediction for muscarinic acetylcholine receptor M1 (P11229) · a predicted model of the same protein · chain A against A, TM-score 0.67

Analyse

• Open in the research workbench: secondary structure, accessibility, pockets, interfaces, conservation, variants, modifications, peptides and crosslinks on the 3D structure
• Every structure of UniProt P11229
• Every structure of UniProt P00720
• Elsewhere: RCSB PDB 5CXV · PDBe 5CXV · UniProt P11229 · UniProt P00720